a versatile optical pump–soft X-ray probe facility with 100 fs X-ray pulses of variable polarization

Here the major upgrades of the femtoslicing facility at BESSY II (Khan et al., 2006) are reviewed, giving a tutorial on how elliptical-polarized ultrashort soft X-ray pulses from electron storage rings are generated at high repetition rates. Employing a 6 kHz femtosecond-laser system consisting of two amplifiers that are seeded by one Ti:Sa oscillator, the total average flux of photons of 100 fs duration (FWHM) has been increased by a factor of 120 to up to 106 photons s-1 (0.1% bandwidth)-1 on the sample in the range from 250 to 1400 eV. Thanks to a new beamline design, a factor of 20 enhanced flux and improvements of the stability together with the top-up mode of the accelerator have been achieved. The previously unavoidable problem of increased picosecond- background at higher repetition rates, caused by `halo' photons, has also been solved by hopping between different `camshaft' bunches in a dedicated fill pattern (`3+1 camshaft fill') of the storage ring. In addition to an increased X-ray performance at variable (linear and elliptical) polarization, the sample excitation in pump-probe experiments has been considerably extended using an optical parametric amplifier that supports the range from the near-UV to the far-IR regime. Dedicated endstations covering ultrafast magnetism experiments based on time-resolved X-ray circular dichroism have been either upgraded or, in the case of time-resolved resonant soft X-ray diffraction and reflection, newly constructed and adapted to femtoslicing requirements. Experiments at low temperatures down to 6 K and magnetic fields up to 0.5 T are supported. The FemtoSpeX facility is now operated as a 24 h user facility enabling a new class of experiments in ultrafast magnetism and in the field of transient phenomena and phase transitions in solids

Identification of Y-Box Binding Protein 1 As a Core Regulator of MEK/ERK Pathway-Dependent Gene Signatures in Colorectal Cancer Cells

Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties

Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial

Background: Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We therefore aimed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis. Methods: In 2001, we designed a multicentre, double-blind, randomised, parallel-group trial, termed the methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN) study. Patients were recruited between October, 2002, and March, 2005 from 50 neurology departments in eight countries. We included treatment-naive patients with relapsing-remitting multiple sclerosis who had an expanded disability status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets. Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained over 6 months. All patients who received at least one dose of study drug were included in all planned analyses. This trial is registered with ClinicalTrials.gov, NCT00168766. Findings: 341 patients were randomly assigned to methylprednisolone (n=172) or placebo (n=169); 171 patients in the methylprednisolone group and 167 in the placebo group received at least one dose of study drug. 90 patients had sustained disability progression: 44 of 167 in the methylprednisolone group and 46 of 171 in the placebo group. The time to sustained progression did not differ between groups (hazard ratio 0·879, 95% CI 0·566-1·365; p=0·57). There were 1436 adverse events, 24 of which were serious, in the methylprednisolone group and 1070 events, 35 of which were serious, in the placebo group. Interpretation: Monthly pulses of methylprednisolone in combination with interferon beta-1a do not seem to affect disability progression any more than interferon beta-1a treatment alone. More research is required to assess whether this treatment regimen might benefit particular subsets of patients. Funding: Biogen Idec. © 2010 Elsevier Ltd. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Dosage effect of zero to three functional LBR-genes in vivo and in vitro

The Lamin B receptor (LBR) is a pivotal architectural protein in the nuclear envelope. Mutations in the Lamin B receptor lead to nuclear hyposegmentation (Pelger-Huët anomaly). We have exactly quantified the nuclear lobulation in neutrophils from individuals with 0, 1, 2 and 3 functional copies of the lamin B receptor gene and analyzed the effect of different mutation types. Our data demonstrate that there is a highly significant gene-dosage effect between the gene copy number and the nuclear segmentation index of neutrophils. This finding is paralleled by a dose-dependent increase in LBR protein and staining intensity of the nuclear membrane in corresponding lymphoblastoid cell lines, which demonstrates a significant correlation on the protein level as well. We further show that LBR expression continually increases during granulopoiesis in vitro from human precursor cells with ovoid nuclei to multi-segmented neutrophil nuclei 11 days later, indicating relevance for regular human granulopoiesis. Altogether, LBR is a unique model that will allow the systematic study of gene-dosage effects and of modifying endogeneous and exogeneous factors on granulopoiesis

Erfahrungen und Empfehlungen aus der Beratung bei Datenmanagementplänen

Datenmanagementpläne werden zunehmend zu einem Teil des wissenschaftlichen Forschungsprozesses. Der vorliegende Bericht fasst die Erfahrungen zum Beratungsprozess von Forschenden bei der Erstellung eines Datenmanagementplans durch zentrale oder dezentrale Ansprechpartnerinnen und -partner zusammen. Die Autorinnen und Autoren aus Universitäten und außeruniversitären Forschungseinrichtungen haben darin ihre Expertise aus mehrjähriger Erfahrung zusammengetragen. Die entstandenen Empfehlungen und Best Practices sollen andere Einrichtungen bei der Beratung von Forschenden unterstützen. Der Bericht entstand im Rahmen der DINI/nestor-AG Forschungsdaten in der Unter-AG Datenmanagementpläne, die zum Ziel hat, Wissen, (Weiterbildungs-)Materialien und Erfahrungen zum Thema auszutauschen sowie weiterzuentwickeln. (DIPF/Orig.

Erfahrungen und Empfehlungen aus der Beratung bei Datenmanagementplänen

Datenmanagementpläne werden zunehmend zu einem Teil des wissenschaftlichen Forschungsprozesses. Der vorliegende Bericht fasst die Erfahrungen zum Beratungsprozess von Forschenden bei der Erstellung eines Datenmanagementplans durch zentrale oder dezentrale Ansprechpartnerinnen und -partner zusammen. Die Autorinnen und Autoren aus Universitäten und außeruniversitären Forschungseinrichtungen haben darin ihre Expertise aus mehrjähriger Erfahrung zusammengetragen. Die entstandenen Empfehlungen und Best Practices sollen andere Einrichtungen bei der Beratung von Forschenden unterstützen. Der Bericht entstand im Rahmen der DINI/nestor-AG Forschungsdaten in der Unter-AG Datenmanagementpläne, die zum Ziel hat, Wissen, (Weiterbildungs-)Materialien und Erfahrungen zum Thema auszutauschen sowie weiterzuentwickeln. (DIPF/Orig.

Erfahrungen und Empfehlungen aus der Beratung bei Datenmanagementplänen

Die nachfolgenden Empfehlungen beschreiben die Erfahrungen und Best Practices der Mitglieder der Unterarbeitsgruppe “Datenmanagementpläne” der DINI/nestor-AG Forschungsdaten. Sie sollen als Orientierungs- und Arbeitshilfe dienen und beschreiben mögliche Vorgehensweisen vor, während sowie nach einem Beratungstermin zu Datenmanagementplänen (DMP). Es wird auf die Bedeutung der Anforderungen der Forschungsförderer hingewiesen. Außerdem werden Checklisten, DMP-Templates und -Tools benannt sowie auf einzelne Unterschiede eingegangen. Einen weiteren wichtigen Punkt im Forschungsdatenmanagement und damit auch im DMP stellt die Kostenkalkulation dar. Zum Schluss wird auf die Evaluation von DMPs eingegangen, um die Qualität des DMPs zu prüfen, aus vorangegangenen DMPs zu lernen und die Beratung stetig zu verbessern